Microevolution in the major outer membrane protein OmpA of .

is nowadays a relevant nosocomial pathogen characterized by multidrug resistance (MDR) and concomitant difficulties to treat infections. OmpA is the most abundant outer membrane (OM) protein, and is involved in virulence, host-cell recognition, biofilm formation, regulation of OM stability, permeability and antibiotic resistance. OmpA members are two-domain proteins with an N-terminal eight-stranded β-barrel domain with four external loops (ELs) interacting with the environment, and a C-terminal periplasmic domain binding non-covalently to the peptidoglycan. Here, we combined data from genome sequencing, phylogenetic and multilocus sequence analyses from 975 strains/isolates of the / complex (ACB), 946 from , to explore microevolutionary divergence. Five major variant groups were identified (V1 to V5) in , encompassing 52 different alleles coding for 23 different proteins. Polymorphisms were concentrated in five regions corresponding to the four ELs and the C-terminal end, and provided evidence for intra-genic recombination. variants were not randomly distributed across the . phylogeny, with the most frequent V1(lct)a1 allele found in most clonal complex 2 (CC2) strains and the second most frequent V2(lct)a1 allele in the majority of CC1 strains. Evidence was found for assortative exchanges of alleles not only between separate . lineages, but also different ACB species. The overall results have implications for evolution, epidemiology, virulence and vaccine design.